Anti aging and Sirtuins

For years people have been in search for that fountain of youth which will keep them young all their lives. They tried looking for it in diet programmes, in exercises, by restricting calories, etc. This forced the scientists to find ways where one could enjoy the benefits of dieting without having to cut down on their calories. What could befool the body into believing that it was consuming restricted calories? A proposition where one could have his cake and eat it too.

In the mid 1990s a professor at M.I.T., Dr. Leonard P. Guarente while studying about yeasts realized that when smaller amounts of food was administered to them it extended their lifespan. He conducted experiments with different sets of genes and found that a certain kind of gene when administered to them, increased their lifespan and its withdrawal led to its death. He named this particular gene Sirt2. This gene improved the performance of the cell by curbing the production of its waste matter. On repeating this experiment with roundworms he got the same result. But as humans did not possess this gene, he found another gene which mimicked SIRT2. He called it Sirt1. These genes suppress certain genes and repair the DNA within the body. This process called 'Gene Silencing' is important to prevent wrong genes from getting activated to protect the functions of the cell. This may probably be one of the causes for Alzheimer's and Type 2 Diabetes which occur due to genetic malfunction. The same is the case with cancer, old age and diseases of the heart. So Antiaging and sirtuins go hand in hand with calorie restriction.

Another important research done in the University of Wisconsin- Madison has discovered that a family of enzymes called 'Sirtuins' plays a very major role in anti-aging. It was in 2001 that scientists started concentrating on its anti aging effects and it was evident that Sirtuins and Lifespan extension were directly linked with each other.

As further researches were conducted, many biotechnology companies dealing in drugs recognized the huge potential of sirtuins as anti-aging drugs and also the alternative treatment for Type2 diabetes and neurological disorders like Alzheimers which are age-related diseases. But for those who want to get rid of wrinkles, sirtuins is a revolution in all anti-aging skin care treatments and development of drugs used to increase the longevity and quality of life by preventing geriatric diseases.

This anti-aging enzyme has been tested so far on yeast, flies and worms in laboratories. It is believed that a high restricted calorie diet increases longevity and this anti-aging enzyme has the same effect on all organisms tested so far. From the various compounds tested for longevity, resveratrol was found to be the most potent anti ageing enzyme, which is a very important ingredient in red wine that lowers the rate of heart disease. Scientists believe that Anti-aging and sirtuins go hand in hand and they are the main regulators of aging found universally in all living organisms and hence are the main targets for anti-aging drugs.

According to David Sinclair a research scholar in Harvard Medical School, 'sirtuins serve as guardians of the cell', and 'These enzymes allow cells to survive damage and delay cell death'. The time has come to look for more such sirtuin stimulators or create synthetic ones so that they can be tested on humans, mice and monkeys after being experimented on smaller organisms like flies, cells and worms.

Researchers have found that if animals are kept on a restricted diet which is nutritious but has fewer calories, their lifespan increases by around 50%. But this can be possible only in the presence of sirtuins. If the animals have been genetically altered, these enzymes become ineffective.

With time the importance of sirtuins is becoming evident to the scientists who believe that they restrict the cellular cycle of old cells which tend to destroy themselves, by beefing up their DNA structure and rejuvenating them. This process acts as a stimulant to produce more protective antioxidants. This was done by introducing such nutritional substances which are low in calories along with simple compounds like resveratrol which increased sirtuin activity. With the addition of these compounds to yeasts, they multiplied by 70%.

Most developing countries are facing the threat of age related diseases. Healthcare providers are facing the pressure of providing alternatives of extending the lifespan without compromising with the quality of life by delaying the onset of age related diseases.

Although with the restricted knowledge that we have with regards to Anti-ageing medications for extending lifespan in humans are sparsely available. Calorie restrictions can help in extending the longevity in humans and cure type2 diabetes by effecting the insulin sensitivity and glucose homeostasis.

An increased activity of SIRT1 enhances the functions of proteins mimicking the effects of calorie restriction. This in turn improves energy levels in the body protecting the body from age related diseases. This information can be used

  • For developing life extending drugs for humans.
  • For delaying the onset of age related diseases like stroke, cancer, Parkinson's and Alzheimer's.
  • For influencing the metabolism and energy balance inType2 Diabetes.

Calorie restriction can be effective in increasing the lifespan only in the presence of sirtuins, SIRT1 and 2. This becomes possible when the increased amount of NAD (nicotinamide adenine dinucleotide) in each cell owing to calorie restriction stimulates activity in SIRT1 and SIRT2. The health providers have now to look for an alternative for NAD, which can be used as a drug or a pill and help us in maintaining a healthy life without calorie restrictions. In this way we can have the cake and eat it too.

Resveratrol is one such drug found in the skin of grapes which is a sirtuin regulator. Experiments conducted on mice have proved that resveratrol increases the lifespan inspite if a high calorie diet thus ascertaining the fact that resveratrol can activate anti aging genes.

Researchers are now trying to use resveratrol to reverse the effects of lung damage caused by excessive smoking. A research in the University of Rochester has discovered that the toxins present in cigarettes destroy the SIRT1 gene which plays a very important role in preventing premature aging. This exposes the lungs to destructive inflammation and lung cancer. Resveratrol is being effectively used in coping up with pulmonary diseases and healing lungs.

According to Dr.Irfan Rahman, associate professor of Environmental Science in the University of Rochester, 'This novel protein will allow us to program our body's immune-inflammatory system against lung damage and premature aging. The hallmark of this discovery is that we may be able to provide remedies to millions of smokers who would like to quit but cannot kick their addiction, and millions of former smokers who, despite quitting, remain at risk for illness as they age'.

Around 23 million Americans suffer from COPD (Chronic Obstructive Pulmonary Disease) which is caused due to inflammation ending up in breathlessness. It is believed that it will become the 3rd leading cause of death throughout the world by the year 2020.

Sirt1 belongs to those genes which regulate and control chronic inflammation, aging and cancer. Higher activation of SIRT1 increases the life span of worms, and fruit flies. It is also effective in stress resistance, apoptosis, metabolism and other premature aging processes.

As the saying goes a little stress is good for the heart and now research also says that a little stress can delay aging. Exposure to heat and cold can damage proteins causing cell death. But cells can combat stresses with a damage limiting mechanism called ‘heat shock response,’ by which special proteins repair the damaged proteins thus extending their lives.

In humans this heat shock response is regulated by SIRT1, a protein related with age and longevity. Mild stresses activate the heat shock response without harming the cells. A calorie restricted diet is one such mild stress that can activate heat shock response. Research has proved beyond doubt that mild stresses have prolonged the span of life in all species that have been tested so far. Anti aging is affected by calorie restricted diets which increase the level of SIRT1 which is protein related with aging.

Whenever a cell is under stress, the heat shock factor steps up the production of molecules which prepare proteins, by latching on to a DNA. When these molecules are produced in abundance, the damage limiting mechanism shuts off by the addition of an acetyl group which is a chemical to the heat shock factor 1, which makes it fall off the DNA strand. But SIRT1 removes the acetyl groups from the heat shock factor1 allowing it to produce more protein repair molecules.

With age the heat shock response is reduced as SIRT1 decreases in the cells. As a result older cells find it difficult to cope up with damage due to stress. Efforts are being made by research to be able to activate heat shock response on demand with the help of SIRT1. Probably that might prove to be a cure for neurodegenerative diseases like Alzheimer's as heat shock response could effectively repair the damaged brain proteins.